Euglycemic Ketoacidosis Causes

Go to: Introduction Hyperglycemia and ketosis in diabetic ketoacidosis (DKA) are the result of insulin deficiency and an increase in the counterregulatory hormones glucagon, catecholamines, cortisol, and growth hormone. Three processes are mainly responsible for hyperglycemia: increased gluconeogenesis, accelerated glycogenolysis, and impaired glucose utilization by peripheral tissues. This might also be augmented by transient insulin resistance due to hormone imbalance, as well as elevated free fatty acids.[1] DKA is most commonly precipitated by infections. Other factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and illicit drug use. The diagnostic criteria of DKA, established by the American Diabetic Association, consists of a plasma glucose of >250 mg/dL, positive urinary or serum ketones, arterial pH of <7.3, serum bicarbonate <18 mEq/L, and a high anion gap. The key diagnostic feature of DKA is elevated circulating total blood ketone concentration. Hyperglycemia is also a key diagnostic criterion of DKA; however, a wide range of plasma glucose levels can be present on admission.
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Diabetic Ketoacidosis (dka)

Tweet Diabetic ketoacidosis (DKA) is a dangerous complication faced by people with diabetes which happens when the body starts running out of insulin. DKA is most commonly associated with type 1 diabetes, however, people with type 2 diabetes that produce very little of their own insulin may also be affected. Ketoacidosis is a serious short term complication which can result in coma or even death if it is not treated quickly. Read about Diabetes and Ketones What is diabetic ketoacidosis? DKA occurs when the body has insufficient insulin to allow enough glucose to enter cells, and so the body switches to burning fatty acids and producing acidic ketone bodies. A high level of ketone bodies in the blood can cause particularly severe illness. Symptoms of DKA Diabetic ketoacidosis may itself be the symptom of undiagnosed type 1 diabetes. Typical symptoms of diabetic ketoacidosis include: Vomiting Dehydration An unusual smell on the breath –sometimes compared to the smell of pear drops Deep laboured breathing (called kussmaul breathing) or hyperventilation Rapid heartbeat Confusion and disorientation Symptoms of diabetic ketoacidosis usually evolve over a 24 hour period if blood glucose levels become and remain too high (hyperglycemia). Causes and risk factors for diabetic ketoacidosis As noted above, DKA is caused by the body having too little insulin to allow cells to take in glucose for energy. This may happen for a number of reasons including: Having blood glucose levels consistently over 15 mmol/l Missing insulin injections If a fault has developed in your insulin pen or insulin pump As a result of illness or infections High or prolonged levels of stress Excessive alcohol consumption DKA may also occur prior to a diagnosis of type 1 diabetes. Ketoacidosis can occasional
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Correspondence Address: Monish S Raut Department of Cardiac Anesthesiology, Sir Ganga Ram Hospital, New Delhi - 110 060 India Source of Support: None, Conflict of Interest: None DOI: 10.4103/ija.IJA_359_17 How to cite this article: Raut MS, Maheshwari A. Euglycemic diabetic ketoacidosis by sodium glucose co-transporter inhibitors: Real but preventable concern. Indian J Anaesth 2017;61:524 Sir, We are thankful for the comments on 'Sodium glucose co-transporter (SGLT2) inhibitor: Patient safety and clinical importance', and we appreciate the concern raised for its risk of euglycemic diabetic ketoacidosis (DKA). During clinical development programs for a new drug approval, it is not uncommon that some unexpected safety issues may go unobserved. Interestingly, the incidence of ketoacidosis for three SGLT2 inhibitors empagliflozin, dapagliflozin and canagliflozin were 0.1%, 0.1% and 0.5%–0.8% in EMPA-REG Outcome trial, DECLARE trial and CANVAS trial, respectively. This is suggestive of acceptably very low occurrence.[1] Ketosis results from lack of insulin causing decreased glucose utilisation by tissues and raised lipolysis leading to free fatty acid (FFA) oxidation and yielding of ketone bodies. In hyperglycaemic DKA, there is marked hyperglycaemia (350–800 mg/dL), profuse glycosuria (2–4 mg/min/kg) and elevated ketone bodies (plasma β-hydroxybutyrate 4.2–11.0 mmol/L).[2] Euglycemic DKA was originally defined as ketoacidosis with plasma glucose levels <300 mg/dL.[3] The primary cause for euglycemic DKA was decreased availability of carbohydrate due to renal loss along with concurrent reduced insulin dose. Although the risk of ketoacidosis is low, clinicians need to be made aware that such risk may become significant in certain situations such as the perioperative
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Euglycemic Ketoacidosis

The purpose of this ariticle is to highlight the importance of not relying exclusively on blood glucose measurements when assessing sick type I diabetics. Urinary ketones and venous bicarbonate are essential in making the diagnosis of relatively low blood glucose plus ketoacidosis, that we call euglycaemic ketoacidosis. Pak J Med Sci January - March 2008 Vol. 24 No. 1 161-162 1. Dr. Muhammad Shahzad Rauf, MBBS, MRCP, Core Medical Training Aberdeen Royal Infirmary, * Received for Publication: October 31, 2007 The condition is defined as diabetic ketoacidosis with a bicarbonate level of less than 10mEq/L and a glucose level of less than 16.7mmol/l or 300mg% along with ketonemia or ketonuria, Euglycemic ketoacidosis occurred in 30% of patients admitted to the hospital on account of diabetic ketoacidosis. 1 True euglycaemic ketoacidosis (initial blood glucose 10mmol/l (180mg%) or less) is rare, occurring in 0.81.1% of all episodes depending on the defining plasma bicarbonate concentration.2 Clinically Euglycaemic ketoacidosis is usually manifested by vomiting. In addition some patient can present with, abdominal pain dysuria, productive cough, thirst, nausea. The cause of preserved "euglycemia" could be greater urinary loss of glucose triggered by counter-regulatory hormones or decreased rate of hepatic glucose production observed during a fast. It has also been demonstrated that the key path physiologic determinant is the quantity of food ingested prior to development of diabetic ketoacidosis: When patients are well fed, their liver contains large amounts of glycogen, which primes it to make glucose and to suppress ketogenesis. However, when patients have been vomiting and unable to eat, the liver is depleted of glycogen and primed to produce ketones. Thus, patients with
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The Case At Hand Recently, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis (DKA) with uncharacteristically mild to moderate glucose elevations (euglycemic DKA [euDKA]) associated with the use of all the approved sodium–glucose cotransporter 2 (SGLT2) inhibitors (1). This Communication was based on 20 clinical cases requiring hospitalization captured between March 2013 and June 2014 in the FDA Adverse Event Reporting System database. The scarce clinical data provided suggested that most of the DKA cases were reported in patients with type 2 diabetes (T2D), for whom this class of agents is indicated; most likely, however, they were insulin-treated patients, some with type 1 diabetes (T1D). The FDA also identified potential triggering factors such as intercurrent illness, reduced food and fluid intake, reduced insulin doses, and history of alcohol intake. The following month, at the request of the European Commission, the European Medicines Agency (EMA) announced on 12 June 2015 that the Pharmacovigilance Risk Assessment Committee has started a review of all of the three approved SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to evaluate the risk of DKA in T2D (2). The EMA announcement claimed that as of May 2015 a total of 101 cases of DKA have been reported worldwide in EudraVigilance in T2D patients treated with SGLT2 inhibitors, with an estimated exposure over 0.5 million patient-years. No clinical details were provided except for the mention that “all cases were serious and some required hospitalisation. Although [DKA] is usually accompanied by high blood sugar levels, in a number of these reports blood sugar levels were only moderately increased” (2). Wit
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Euglycemic Diabetic Ketoacidosis With Acute Pancreatitis In A Patient Not Known To Have Diabetes

Diabetic ketoacidosis (DKA) is usually easily recognized and is characterized by hyperglycemia, metabolic acidosis, and increased ketones (1). Euglycemic DKA, a relatively uncommon presentation, is a less known entity and can go unrecognized at initial presentation. It can be caused by starvation of any cause in conjunction with a current illness (2) and has been described mainly in patients with type 1 diabetes (3,4) but also in subjects with type 2 and gestational diabetes (3,5). We report a case of euglycemic DKA precipitated by starvation and severe pancreatitis in a patient with history of chronic alcoholism and no known underlying diabetes. This case shows the complex interplay among severe alcohol-related pancreatic injury, ketoacidosis, and starvation physiology. It highlights the fact that euglycemic DKA should be considered in the differential diagnosis of an ill patient presenting with metabolic acidosis, even in the absence of hyperglycemia. A 36-year-old female presented to the emergency room with severe epigastric pain with radiation to her back of 3 days duration and a 1-week history of nausea and vomiting. She reported having not eaten for over 1 week and admitted to drinking 1 L of brandy daily for years; her last drink was 3 days prior to admission. She denied taking any medications. Her medical records review revealed a history of hematemesis from a Mallory-Weiss tear and rehabilitation for alcoholism in 2007 and 2008 with subsequent relapses. Her family history was significant for coronary artery disease, diabetes, and hypertension, and her mother also struggled with alcoholism. Physical examination revealed a temperature of 36.6°C, blood pressure 123/71 mm Hg, respiratory rate 24 per minute, heart rate 80 per minute, oxygen saturation 100% on room
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Euglycemic diabetic ketoacidosis is a post market warning in patients with type 1 diabetes and type 2 diabetes treated with SGLT-2 inhibitors. We report a case of a 39-year-old obese female with presumed type 2 diabetes for seven years who presented to the emergency department with three days of nausea, vomiting, and abdominal pain. Due to previous total non-adherence with a prescribed insulin regimen, she was recently started on canagliflozin and liraglutide. The diagnosis of euDKA was missed in the initial evaluation as the blood glucose level was only 167 mg/dL. Further work up showed severe metabolic acidosis with an anion gap of 25 and positive ketones in the urine. She was treated successfully with dextrose water 5%/half normal saline and an insulin drip. As part of the work up, she tested positive for glutamic acid decarboxylase autoantibodies. Given the increasing utilization of SGLT-2 inhibitors and the fact that patients can present with near-normal glycemia, the diagnosis can be missed. Vigilance with the use of SGLT-2 inhibitors is necessary to decrease morbidity and potentially mortality particularly in patients with long-standing type 2 diabetes associated with marked β-cell insufficiency, type 1 diabetes mellitus, or latent autoimmune diabetes of adult onset.
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Objective Sodiumglucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. Research Design and Methods Cases identified incidentally are described. Results We identified 13 episodes of SGLT-2 inhibitorassociated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. Conclusions SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes. Sodiumglucose cotransporter 2 (SGLT-2) inhibitors are the newest class of antihyperglycemic medications, first marketed in 2013 for the treatment of type 2 diabetes.[ 1 ] Limited studies suggest that SGLT-2 inhibitors may be effective in addressing many of the unmet needs of people with type 1 diabetes, including improving average glycemia, while reducing glycemic variability and postprandial hyperglycemia, without increasing hypoglycemia, as well as promoting weight loss while reducing insulin doses.[ 28
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Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus.[1] Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion, and occasionally loss of consciousness.[1] A person's breath may develop a specific smell.[1] Onset of symptoms is usually rapid.[1] In some cases people may not realize they previously had diabetes.[1] DKA happens most often in those with type 1 diabetes, but can also occur in those with other types of diabetes under certain circumstances.[1] Triggers may include infection, not taking insulin correctly, stroke, and certain medications such as steroids.[1] DKA results from a shortage of insulin; in response the body switches to burning fatty acids which produces acidic ketone bodies.[3] DKA is typically diagnosed when testing finds high blood sugar, low blood pH, and ketoacids in either the blood or urine.[1] The primary treatment of DKA is with intravenous fluids and insulin.[1] Depending on the severity, insulin may be given intravenously or by injection under the skin.[3] Usually potassium is also needed to prevent the development of low blood potassium.[1] Throughout treatment blood sugar and potassium levels should be regularly checked.[1] Antibiotics may be required in those with an underlying infection.[6] In those with severely low blood pH, sodium bicarbonate may be given; however, its use is of unclear benefit and typically not recommended.[1][6] Rates of DKA vary around the world.[5] In the United Kingdom, about 4% of people with type 1 diabetes develop DKA each year, while in Malaysia the condition affects about 25% a year.[1][5] DKA was first described in 1886 and, until the introduction of insulin therapy in the 1920s, it was almost univ
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Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma 1Department of Internal Medicine, Memorial Hospital of Martinsville and Henry County, Martinsville, Virginia, USA, 2Texas Tech University Health Sciences Center, El Paso, Texas, USA, 3Senior Research Associate, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA, 4Department of Pharmacology, St Johns Medical College, Bangalore, India, Received 2017 Jul 18; Accepted 2017 Aug 4. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License . Euglycemic diabetic ketoacidosis (EDKA) is a clinical triad comprising increased anion gap metabolic acidosis, ketonemia or ketonuria and normal blood glucose levels <200 mg/dL. This condition is a diagnostic challenge as euglycemia masquerades the underlying diabetic ketoacidosis. Thus, a high clinical suspicion is warranted, and other diagnosis ruled out. Here, we present two patients on regular insulin treatment who were admitted with a diagnosis of EDKA. The first patient had insulin pump failure and the second patient had urinary tract infection and nausea, thereby resulting in starvation. Both of them were aggressively treated with intravenous fluids and insulin drip as per the protocol for the blood glucose levels till the anion gap normalized, and the metabolic acidosis reversed. This case series summarizes, in brief, the etiology, pathophysiology and treatment of EDKA. Euglycemic diabetic ketoacidosis is rare. Consider ketosis in patients with DKA even if their serum glucose levels are normal. High clinical suspicion is required to diagnose EDKA as normal blood sugar levels masquerade the underlying DKA and cause a diagnostic and therapeutic dilemma. Blood pH and blood or urine
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Euglycemic Diabetic Ketoacidosis Sometimes Seen With Sglt2 Inhibitors

Euglycemic Diabetic Ketoacidosis Sometimes Seen with SGLT2 Inhibitors Diabetic ketoacidosis (DKA) in patients with presenting serum blood glucose <200 mg/dL isnt common. More often, its seen in patients with type 1 diabetes in conjunction with starvation and acute illness.1 Its difficult to determine an incidence of euglycemic DKA (euDKA) among all DKA cases in the literature, given the migration of the serum glucose cutoff from 300 mg/dL to 200 mg/dL. The best estimation based on an analysis of case reports suggests an incidence anywhere between 0.8% and 7.5%.1 However, the sodium-glucose cotransporter-2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin can apparently induce this once-rare form of DKA.2,3 SGLT2 inhibitors are a class of oral hypoglycemic drugs indicated only for type 2 diabetes. Their novel mechanism of action prevents glucose reabsorption from the proximal renal tubules, resulting in increased glucosuria and decreasing plasma glucose. SGLT2 inhibitors lower serum glucose and HBA1C levels, and even produce weight loss. However, the increased glucose concentration in the bladder is a terrific incubation environment for fungi and bacteria, so much so that the FDA stuck a post-marketing warning on the drug class for the increased risk of serious urinary tract infections and urosepsis, in addition to euglycemic DKA. The proposed mechanism suggests that while SGLT2 inhibitors lower serum glucose, they also reduce insulin secretion from pancreatic beta cells in a negative feedback fashion. The lower serum insulin coupled with lower serum glucose consequently shifts energy metabolism to antilipolytic activity, and thus free fatty acid (FFA) oxidation and ketosis. Its been postulated that this SGLT2 inhibitor-induced insulin deficiency may pr
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